Minimally Invasive and Conservative Interventions for the Treatment of Sacroiliac Joint Pain: A Review of Recent Literature.

Sacroiliac joint (SIJ) pain is responsible for approximately a third of reported back pain. Patients with SIJ pain report some of the lowest quality of life scores of any chronic disease. Understanding of the physiology and pathology of the SI joint has changed dramatically over the years, and SI joint pain and injury can now be thought of in two broad categories: traumatic and atraumatic. Both categories of SI joint injury are thought to be caused by inflammation or injury of the joint capsule, ligaments, or subchondral bone in the SI joint. Treatment of SI joint pain usually involves a multi-pronged approach, utilizing both, multi-modal medical pain control and interventional pain/surgical techniques such as steroid injections, radiofrequency nerve ablation, and minimally invasive sacroiliac arthrodesis. Though conservative management through multi-modal pain control and physical therapy have their role as first line therapies, an increasing body of evidence supports the use of minimally invasive procedures, both as adjuvant treatments to conservative management and as second line therapies for patient's that fail first line treatment.

Minimally Invasive and Conservative Interventions for the Treatment of Sacroiliac Joint Pain: A Review of Recent Literature.

Sacroiliac joint (SIJ) pain is responsible for approximately 15-25% of reported back pain. Patients with SIJ pain report some of the lowest quality of life scores of any chronic disease. Understanding of the physiology and pathology of the SI joint has changed dramatically over the years, and SI joint pain and injury can now be thought of in two broad categories: traumatic and atraumatic. Both categories of SI joint injury are thought to be caused by inflammation or injury of the joint capsule, ligaments, or subchondral bone in the SI joint. Treatment of SI joint pain usually involves a multi-pronged approach, utilizing both, multi-modal medical pain control and interventional pain/surgical techniques such as steroid injections, radiofrequency nerve ablation, and minimally invasive sacroiliac arthrodesis. Though conservative management through multi-modal pain control and physical therapy have their role as first line therapies, an increasing body of evidence supports the use of minimally invasive procedures, both as adjuvant treatments to conservative management and as second line therapies for patient's that fail first line treatment.

Inotersen to Treat Polyneuropathy Associated with Hereditary Transthyretin (hATTR) Amyloidosis.

Background: Amyloidosis is a group of diseases with the common pathophysiology of protein misfolding and aberrant deposition in tissue. There are both acquired and hereditary forms of this disease, and this review focuses on the latter hereditary transthyretin-mediated (hATTR). hATTR affects about 50,000 individuals globally and mostly appears as one of three syndromes - cardiac, polyneuropathy, and oculoleptomeningeal. Polyneuropathy is the most common form, and there is usually some overlap in individual patients. Results: Recently, novel therapeutic options emerged in the form of groundbreaking drugs, Patisiran and Inotersen, small interfering RNA molecules that target TTR and reduce the production of this protein. By targeting TTR mRNA transcripts, Inotersen decreases protein translation and production, reducing the deposition of misfolded proteins. It was shown to be both effective and safe for use and specifically formulated to concentrate in the liver - where protein production takes place. Conclusion: hATTR is a rare, progressive, and debilitating disease. Its most common presentation is that of polyneuropathy, and it carries a very poor prognosis and a natural history conveying a median survival of < 12 years. Novel therapeutic options are groundbreaking by providing disease-modifying specific, targeted therapies against TTR production and deposition. The use of RNA interference (RNAi) opens the door to the treatment of hereditary diseases by targeting them at the genetic level.

Efficacy of Chemical and Biological Stump Treatments for the Control of Heterobasidion occidentale Infection of California Abies concolor.

We conducted an experimental evaluation of treatments to limit Heterobasidion occidentale infection of white fir (Abies concolor) stumps and wounds in California mixed conifer forests. We tested the efficacy of urea, borate, and a mixture of two locally collected Phlebiopsis gigantea strains in preventing pathogen colonization of fir stumps and separately, urea and borate as infection controls on experimental stem wounds. These were paired with a laboratory test on ~100 g wood blocks with and without a one-week delay between inoculation and treatment. Urea, borates, and Phlebiopsis treatments all significantly reduced the stump surface area that was colonized by H. occidentale at 84%, 91%, and 68%, respectively, relative to the controls. However, only the borate treatments significantly lowered the number of stumps that were infected by the pathogen. The laboratory study matched the patterns that were found in the stump experiment with a reduced area of colonization for urea, borates, or P. gigantea treatments relative to the controls; delaying the treatment did not affect efficacy. The field wound experiment did not result in any Heterobasidion colonization, even in positive control treatments, rendering the experiment uninformative. Our study suggests treatments that are known to limit Heterobasidion establishment on pine or spruce stumps elsewhere in the world may also be effective on true firs in California.

Milnacipran for the Treatment of Fibromyalgia.

PURPOSE OF REVIEW: This is a comprehensive review of the literature regarding the use of milnacipran in treating fibromyalgia. A chronic pain disorder with other system disturbances, fibromyalgia is often resistant to many therapeutic approaches. This review presents the background, evidence, and indications for using milnacipran as a treatment option for this condition. RECENT FINDINGS: The definition of fibromyalgia has evolved over many years as it is a relatively tricky syndrome to measure objectively. Today, it is characterized by chronic, widespread pain accompanied by alterations in sleep, mood, and other behavioral aspects. A variety of therapeutic regimens currently used to treat the syndrome as a singular approach are rarely effective.Milnacipran is one of three drugs currently approved by the FDA for the treatment of fibromyalgia. It acts as a serotonin and norepinephrine reuptake inhibitor, which results in decreased pain transmission. Milnacipran remains an effective treatment option for fibromyalgia in adults and needs to be further evaluated with existing therapeutic approaches. SUMMARY: Fibromyalgia is a broad-spectrum disorder primarily characterized by chronic pain coupled with disturbances in cognitive functioning and sleep. The progression of this syndrome is often debilitating and significantly affects the quality of life. Milnacipran is one of three FDA-approved drugs used to alleviate the symptom burden and is comparatively more therapeutic in specific domains of fibromyalgia. A more holistic approach is needed to treat fibromyalgia effectively and further research, including direct comparison studies, should be conducted to fully evaluate the usefulness of this drug.

Landscape epidemiology and control of pathogens with cryptic and long-distance dispersal: sudden oak death in northern Californian forests.

Exotic pathogens and pests threaten ecosystem service, biodiversity, and crop security globally. If an invasive agent can disperse asymptomatically over long distances, multiple spatial and temporal scales interplay, making identification of effective strategies to regulate, monitor, and control disease extremely difficult. The management of outbreaks is also challenged by limited data on the actual area infested and the dynamics of spatial spread, due to financial, technological, or social constraints. We examine principles of landscape epidemiology important in designing policy to prevent or slow invasion by such organisms, and use Phytophthora ramorum, the cause of sudden oak death, to illustrate how shortfalls in their understanding can render management applications inappropriate. This pathogen has invaded forests in coastal California, USA, and an isolated but fast-growing epidemic focus in northern California (Humboldt County) has the potential for extensive spread. The risk of spread is enhanced by the pathogen's generalist nature and survival. Additionally, the extent of cryptic infection is unknown due to limited surveying resources and access to private land. Here, we use an epidemiological model for transmission in heterogeneous landscapes and Bayesian Markov-chain-Monte-Carlo inference to estimate dispersal and life-cycle parameters of P. ramorum and forecast the distribution of infection and speed of the epidemic front in Humboldt County. We assess the viability of management options for containing the pathogen's northern spread and local impacts. Implementing a stand-alone host-free "barrier" had limited efficacy due to long-distance dispersal, but combining curative with preventive treatments ahead of the front reduced local damage and contained spread. While the large size of this focus makes effective control expensive, early synchronous treatment in newly-identified disease foci should be more cost-effective. We show how the successful management of forest ecosystems depends on estimating the spatial scales of invasion and treatment of pathogens and pests with cryptic long-distance dispersal.

Lessons learned from a decade of Sudden Oak Death in California: evaluating local management.

Sudden Oak Death has been impacting California's coastal forests for more than a decade. In that time, and in the absence of a centrally organized and coordinated set of mandatory management actions for this disease in California's wildlands and open spaces, many local communities have initiated their own management programs. We present five case studies to explore how local-level management has attempted to control this disease. From these case studies, we glean three lessons: connections count, scale matters, and building capacity is crucial. These lessons may help management, research, and education planning for future pest and disease outbreaks.

The "aqueous" Prins reaction.

[reaction: see text] In this communication we demonstrate that Prins cyclization reactions occur under very mild conditions when cyclic alpha,beta-unsaturated acetals are employed as oxocarbenium ion progenitors and allylsilanes are used as nucleophiles. Cyclizations proceed efficiently inside Lewis acidic micelles in water, demonstrating that colloidal suspensions can protect highly electrophilic intermediates from hydrolysis. Reactions are experimentally facile and useful in the preparation of a variety of vinyl- and aryl-substituted tetrahydropyrans with excellent stereocontrol.

Deficiency of either cyclooxygenase (COX)-1 or COX-2 alters epidermal differentiation and reduces mouse skin tumorigenesis.

Nonsteroidal anti-inflammatory drugs are widely reported to inhibit carcinogenesis in humans and in rodents. These drugs are believed to act by inhibiting one or both of the known isoforms of cyclooxygenase (COX). However, COX-2, and not COX-1, is the isoform most frequently reported to have a key role in tumor development. Here we report that homozygous deficiency of either COX-1 or COX-2 reduces skin tumorigenesis by 75% in a multistage mouse skin model. Reduced tumorigenesis was observed even though the levels of stable 7,12-dimethylbenz(a)anthracene-DNA adducts were increased about 2-fold in the COX-deficient mice compared with wild-type mice. The premature onset of keratinocyte terminal differentiation appeared to be the cellular event leading to the reduced tumorigenesis because keratin 1 and keratin 10, two keratins that indicate the commitment of keratinocytes to differentiate, were expressed 8-13-fold and 10-20-fold more frequently in epidermal basal cells of the COX-1-deficient and COX-2-deficient mice, respectively, than in wild-type mice. Papillomas on the COX-deficient mice also displayed the premature onset of keratinocyte terminal differentiation. However, loricrin, a late marker of epidermal differentiation, was not significantly altered, suggesting that it was the early stages of keratinocyte differentiation that were primarily affected by COX deficiency. Because keratin 5, a keratin associated with basal cells, was detected differently in papillomas of COX-1-deficient as compared with COX-2-deficient mice, it appears that the isoforms do not have identical roles in papilloma development. Interestingly, apoptosis, a cellular process associated with nonsteroidal anti-inflammatory drug-induced inhibition of tumorigenesis, was not significantly altered in the epidermis or in papillomas of the COX-deficient mice. Thus, both COX-1 and COX-2 have roles in keratinocyte differentiation, and we propose that the absence of either isoform causes premature terminal differentiation of initiated keratinocytes and reduced tumor formation.